We’ll go to our third type of nephrotic syndrome.
Our first minimal change, second, FSGS,
let’s talk about our membranous glomerulonephritis.
Membranous, as the name implies,
it will be the membrane that will be affected
and depending as to which demographics you’re dealing with,
well, some would say that this is the most common that’s found in adults,
but be careful here, whereas in other demographics in populations and such
would say that FSGS is in adults.
Well, both are true. You have to know both.
If you’re dealing with Hispanic population
and you’re dealing with African-American population, then, you’re looking at in adults,
you’re looking at FSGS being quite common and we talked about HIV patients.
If it is an adult 40 year old approximately Caucasian male,
then you’re thinking at membranous glomerulonephritis, are we clear?
Now, once you get your patient down
and in this patient is a Caucasian male, approximately 40’s coming in,
and they’re presenting with what?
A generalize edema, you’ll have greater than 3.5 grams of protein that’s being lost,
you have lipoid accumulation,
and you know this is membranous maybe may not have hypertension.
High incidence in teenagers, young adults.
There is going to be complete thickening of the membrane.
Membrane, what you do not see here is proliferative, is that clear?
At some point, when we get into MPGN, completely different diagnosis.
Students tend to get that confused.
Don’t do that anymore.
So in H&E, you’ll find the entire glomerulus membrane which is now then become thickened.
Electron microscopy is important for you to understand.
Okay, now, let’s say that you have the membrane that’s being involved, okay, great.
And at the same time, you also find that on the side of the podocyte, where are you?
You’re inside. Underneath that podocyte, you end up finding deposit,
what kind of deposit would you call this? Subepithelial type of deposit.
That you’ll have to memorize please.
So here in membranous glomerulonephritis,
what’s amazing and important clinically is the fact that not only
are you gonna have membrane involvement
into membranous deposition of immunoglobulin, what did I say?
Immunoglobulin, but then, you also have subepithelial deposit.
Now, why is that important?
Because, you’re taking, you're reading your clinical vignette
and you’ve been posed with questions, okay?
And if you weren’t paying attention,
then maybe perhaps you got these two diagnosis confused,
or these three really, watch this.
I want you to tell me in your head you’re thinking three different conditions.
One is membranous glomerulonephritis, the other one is PSGN,
poststreptococcal glomerulonephritis, and the third one is Goodpasture.
Why did I bring up those three?
In membranous, are we affecting the membrane? Absolutely, hence the name.
On light microscopy, you’ll find thickening of that membrane.
In Goodpasture, is it possible that you find thickening of the membrane
or would you find involvement of the membrane in Goodpasture?
Yes, you would.
So now, you have two conditions in which a membrane is involved.
How can you tell the difference? Hold on.
In membranous, take a look at this, you must memorize subepithelial deposit.
In Goodpasture, do you have such immune-complex deposition?
No, you do not in Goodpasture.
That’s a type two hypersensitivity, you do not have such immune-complex deposition.
How can you confirm that? Immunofluorescence, interesting.
Immunofluorescence on Goodpasture, what have you seen? Linear pattern.
If this is subepithelial, then, what’s my pattern? Good, we have a granular pattern.
What was the third differential that I gave you? Poststreptococcal glomerulonephritis.
Why’d I give you this one as being a differential?
In poststreptococcal glomerulonephritis, where is my deposit?
Where is my deposit please? Subepithelial.
Where is my deposit here? Uh-oh, subepithelial.
How can I tell the difference?
Obviously, history, but say that you kind of ignored the history
and all that you’re looking at is electron microscopy, how can you tell the difference?
It’s a fact that here in membranous, you have membrane and subepithelial.
What about poststreptococcal? Only subepithelial, is that understood?
So the three major differentials,
you wanna make sure you come back and review what I just said here
and you’re clear about what to clinch clinically that you make the diagnosis.
Membranous glomerulonephritis has both membrane involvement and subepithelial.
Poststreptococcal, only subepithelial,
obviously coming from the skin or from the pharyngitis
and then we have Goodpasture which is only the membrane, are we clear?
Only after this and you feel solid and comfortable, should you move on.
Now, there is something called spike and dome.
You won’t really be given that but just so that you know.
The spike represents in between the immune-complexes,
you’ll have the intervening glomerular basement membrane
in between the immune-complexes.
What does the immune-complex look like?
It looks like a dome, hence, the spike and dome description.
And granular deposition, sure, why?
And by the way, on what kind of biopsy pattern? Good, Immunofluorescence.
And here, you’ll find IgG or C3 and it will be what kind of deposit?
Subepithelial, membranous glomerulonephritis.
Here, if you take a look at the left light microscopy,
you’ll find the entire glomerulus has been involved
and you find thickening of that membrane, point number one.
Point number two, the figure on the right with electron microscopy,
first and foremost, is the membrane involved? Yes, it is.
Who is your patient?
Most likely a 40-year-old Caucasian male adult, obviously.
And that deposit which is a dark deposit, well, that membrane looks messed up.
What side of this? It looks like it’s the foot process
right and above, so underneath the foot process is a subepithelial deposit.
That is the dome in between the immuno-complexes
or the domes would be the intervening basement membrane.
There is no proliferation here. Membranous glomerulonephritis.
Here, on immunofluorescence, this is a picture in which we’re seeing our granular pattern.
The cartoon then represents membrane involvement
and also, you have issues with subepithelial.
Would you perhaps find foot process being effaced or fused, what is this?
What does that mean to you? Cytokines.
So therefore, what kind of effect may cytokines have on your podocyte?
Fusion, so as a general rule,
fusion of your foot processes could be found in all nephrotic syndromes,
membranous, thickened membrane,
spiked appearance will be the membrane and the dome
in fact would be the subepithelial deposit.
Under membranous, important associations, you wanna keep in mind.
Usually primary, could be secondary.
Now, secondary, be careful.
Drugs, by drugs, I don’t mean heroine.
If it was heroine, you were thinking about FSGS,
if it was HIV, you were thinking about FSGS.
The drugs here, may be chelators, Penicillamine.
May be antihypertensives, -prils, or anti-inflammatory, prescription drugs.
Malignancies are a big one: lung, colon, melanoma, membranous.
SLE, stop here for one second. Do not breeze past this.
SLE and its prototype that we have discussed is which one? Type IV classification.
One, two, three, four, give me a nephritic/nephrotic mixed picture that has four letters in it.
DPGN, what kind of deposit there?
Subendothelial, you’ve heard of the wired loop.
This is 10% of the time with SLE could have membranous.
I told you we would come back and then, we’d discuss this, well, here we go.
So if you find an SLE patient, double stranded DNA, and subepithelial,
this is membranous, is that clear?
Infection, big time, hepatitis B, hepatitis C, be careful though, this is membranous.
The reason I say be careful is because with the hepatitis C virus,
oftentimes associated with a clinical manifestation called cryoglobulinemia,
and that cryoglobulinemia may actually may give you a picture of what’s called MPGN.
We’ll talk more about that later
but I want you to give yourself some important secondary causes,
and metabolic, maybe perhaps diabetes mellitus.
Prognosis, often progresses and rarely responds to steroid therapy.
It can progress to end stage renal disease
and may be associated with renal vein thrombosis.
Renal vein thrombosis not artery, is that clear?
So if it’s renal vein thrombosis and if it’s further distal
especially let’s say that we’re left renal vein, pay attention, left renal vein.
I want you to move from the kidney towards your inferior vena cava, good.
As you move from the left renal vein, there goes my blood.
All of a sudden, there’s thrombus and all of a sudden what should be anastomosing,
your left gonadal vein, you see what I’m getting at now?
So there’s thrombus formation, left renal vein,
and I cannot move towards the inferior vena cava
and you are now blocking the left gonadal vein
in a male would end up having a bag of worms, what’s this called? Varicocele.